We examine robustness to mutations in the nematode worm Caenorhabditis elegans and the role of single‐copy and duplicate genes in it. We do so by integrating complete genome sequence and microarray gene expression data with results from a genome‐scale study using RNA interference (RNAi) to temporarily eliminate the functions of more than 16 000 worm genes. We found that 89% of single‐copy and 96% of duplicate genes show no detectable phenotypic effect in an RNAi knock‐down experiment. We find that mutational robustness is greatest for closely related gene duplicates, large gene families and similarly expressed genes. We discuss the different causes of mutational robustness in single‐copy and duplicate genes, as well as its evolutionary origin.